ABSTRACT
Very low (nano- and subnanomolar) concentrations of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) were found to prolong lifespan of a fungus (Podospora anserina), a crustacean (Ceriodaphnia affinis), an insect (Drosophila melanogaster), and a mammal (mouse). In the latter case, median lifespan is doubled if animals live in a non-sterile vivarium. The lifespan increase is accompanied by rectangularization of the survival curves (an increase in survival is much larger at early than at late ages) and disappearance of typical traits of senescence or retardation of their development. Data summarized here and in the preceding papers of this series suggest that mitochondria-targeted antioxidant SkQ1 is competent in slowing down execution of an aging program responsible for development of age-related senescence.
Subject(s)
Aging/drug effects , Cladocera/drug effects , Drosophila melanogaster/drug effects , Longevity/drug effects , Mitochondria/metabolism , Plastoquinone/pharmacology , Podospora/drug effects , Animals , Biological Transport , Cells, Cultured , Cladocera/physiology , Drosophila melanogaster/physiology , Drosophila melanogaster/ultrastructure , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Male , Mice , Mice, Transgenic , Mitochondria/drug effects , Mitochondria/ultrastructure , Plastoquinone/analogs & derivatives , Plastoquinone/metabolism , Podospora/genetics , Podospora/physiologyABSTRACT
The levels and distribution between nucleus and cytoplasm of HMG1 and HMG2 proteins have been investigated in different tissues of mammals. In lymphoid tissues and testis high amounts of these proteins are present in both nuclei and cytoplasm, while in the hepatic tissues and brain they accumulate in cytoplasm, mainly in the cytosol. In particular, very low amounts, if any, of HMG1 and 2 are present in the nuclei active for DNA replication (rat regenerating liver and primary hepatoma) or transcription (adult liver and brain). Therefore, it appears that HMG1 and 2 are not necessary for these processes. On the other hand, nuclear (chromosomal) HMG1 and 2 are characteristic for the tissues containing undifferentiated cells: lymphoid tissues, testis, neonatal liver. These proteins are bound to the chromatin regions solubilized early by sonication or DNase action. Comparison of the data obtained for different tissues shows an inverse correlation between the amounts of chromosomal HMG1 and 2, on the one hand, and of histone H1(0), on the other hand. These results suggest that chromosomal HMG1 and 2 take part in the processes that occur during cell differentiation, while histone H1(0) is induced to preserve differentiated cells from dedifferentiation.
Subject(s)
Cell Nucleus/metabolism , Cytoplasm/metabolism , High Mobility Group Proteins/metabolism , Animals , Cattle , Electrophoresis, Gel, Two-Dimensional , Electrophoresis, Polyacrylamide Gel , High Mobility Group Proteins/physiology , Histones/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms, Experimental/metabolism , Mammals/metabolism , Organ Specificity , Rats , Subcellular Fractions/metabolism , Swine/metabolismABSTRACT
Five groups of outbred white male rats were given N-nitrososarcosin ethyl ester (NSEE) i.g. for 4 or 6 months at a daily dose of 50 mg/kg of body wt. 5 days/week. Some groups of animals were given a 3% water solution of acetic acid or a 40% solution of ethanol i.g. for 8 months from the beginning of the experiment. The remaining groups of these rats received controlled local thermal burn injury of the esophageal mucosa 15 days before the beginning of the experiment. Acetic acid solution increased the multiplicity of benign and malignant tumors as well as carcinoma incidence in the esophagus. Ethanol in combination with NSEE did not influence carcinogenesis in the esophagus but increased the incidence of leukokeratosis and the multiplicity of forestomach papillomas. In rats treated with NSEE after thermal burn injury, a significant increase in the frequency and multiplicity of papillomas was found in the burn zone.